Thomas Prince
Posters-Accepted Abstracts: Chemotherapy
The merging of knowledge from genomics, cellular signal transduction and molecular evolution is producing a new paradigm of cancer analysis. Tyrosine kinases have long been understood to initiate and promote malignant cell growth. Targeting tyrosine kinases to fight cancer has been a major strategy for the pharmaceutical industry for almost 3 decades. Despite the initial success of tyrosine kinase inhibitors, the ability of cancer to evolve resistance and switch between oncogenic signals has made the effective use of tyrosine kinase inhibitors difficult. The molecular chaperone HSP90 physically supports global tyrosine kinase function while also acting as an evolutionary capacitor. The Cancer Genome Atlas has compiled a trove of data that indicates a number of cancers over-express or possess mutant tyrosine kinases that depend on HSP90 and its cohorts. Targeting HSP90 function could therefore complement tyrosine kinase inhibitors for treating cancer by inhibiting cancer evolution and preventing oncogenic switching. Based on this hypothesis our work has focused on the interplay between tyrosine kinases and the HSP90 molecular chaperone machine with the aim of developing synergistic combinations of molecular therapies to combat cancer.
